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Lipopolysaccharide binding protein and CD14 interaction induces tumor necrosis factor-alpha generation and neutrophil sequestration in lungs after intratracheal endotoxin.

Abstract：

:It has been proposed that lipopolysaccharide (LPS) bound to the 60-kD LPS binding protein (LBP) forms an LPS/LBP complex that, in turn, binds to the CD14 receptor on monocytes/macrophages and stimulates the release of cytokines. We examined the role of LBP and CD14 in tumor necrosis factor-alpha (TNF-alpha) production and neutrophil (polymorphonuclear leukocyte [PMN]) sequestration in lungs induced by intratracheal instillation of LPS using rabbit lungs perfused at constant flow with lactated Ringer-albumin solution. LPS alone (Salmonella minnesota, wild type; 20 ng) or in the presence of LBP (500 ng) was injected intratracheally. In some experiments, human PMNs (5 x 10(7)) were added to the perfusate after a 2-hour period of perfusion. Samples of lung perfusate were collected every 30 minutes for 180 minutes when bronchoalveolar lavage was also performed. TNF-alpha concentrations in the perfusate and bronchoalveolar lavage fluid were determined by use of a bioassay with L-929 fibroblasts, and PMN accumulation in lungs was determined by myeloperoxidase assay of lung homogenates. LPS alone did not significantly increase TNF-alpha production or lung PMN accumulation, whereas the LPS/LBP complex increased TNF-alpha concentration in perfusate twofold and PMN accumulation twofold compared with the effect of LPS alone. Intratracheal instillation of anti-CD14 monoclonal antibody MY4 (40 micrograms) with the LPS/LBP complex prevented TNF-alpha release and PMN sequestration, whereas an isotype-matched control monoclonal antibody was ineffective. Therefore, LBP in the airspace enhances the LPS effect on TNF-alpha production via a CD14-dependent pathway, and as a result, CD14 activation can contribute to lung PMN sequestration.(ABSTRACT TRUNCATED AT 250 WORDS)

journal_name

Circ Res

journal_title

Circulation research

authors

Ishii Y,Wang Y,Haziot A,del Vecchio PJ,Goyert SM,Malik AB

doi

10.1161/01.res.73.1.15

subject

Has Abstract

pub_date

1993-07-01 00:00:00

pages

15-23

issue

eissn

0009-7330

issn

1524-4571

journal_volume

pub_type

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Lipopolysaccharide binding protein and CD14 interaction induces tumor necrosis factor-alpha generation and neutrophil sequestration in lungs after intratracheal endotoxin.